This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The main purpose of this research project is to identify protein biomarkers for both prostate cancer development and progression. Two principal sources are used to achieve this goal. The first is the LNCaP/C4-2/C4-2B xenograft cell model for prostate cancer progression. We have previously used genomic and proteomic approaches to identify novel, previously undescribed factors involved in therapy resisitance and bone metastasis. These include proteins from different areas of cell biochemistry, including signal transduction, cell adhesion, protein transport, and chaperon function. We are currently investigating the exact function of these new factors in promoting prostate cancer. The second source consists of prostatectomy tissue samples, cancerous and matched adjacent, collected at the University New Mexico School of Medicine and the Veterans Affairs Medical Center in Albuquerque. We have so far collected samples from ~150 patients diagnosed with prostatic diseases such as adenocarcinoma and benign hyperplasia. Assessment of markers of genomic instability in these tissues, such as telomere DNA content and allelic imbalance, indicates the presence of genetic and biochemical alterations. We are using genomic and proteomic approaches to characterize these alterations and have identified a number of new leads currently under investigation for their exact function. In particular, proteins found to be altered in histologically normal tissues adjacent to tumors may be biomarkers of early cancer development. We plan to determine the clinical value of newly discovered biomarkers in validation sets of human prostatic tissues in order to develop means of earlier diagnosis and more accurate prognosis for prostate cancer patients.